Palbociclib or Tazemetostat in Combination With CPX-351 for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia
- Registration Number
- NCT05627232
- Lead Sponsor
- Thomas Jefferson University
- Brief Summary
This phase I trial tests the safety, side effects, and best dose of palbociclib or tazemetostat in combination with CPX-351 in treating patients with acute myeloid leukemia (AML) that has come back (relapsed) or does not respond to treatment (refractory). CPX-351 is a combination of the chemotherapy drugs, daunorubicin and cytarabine, which is the standard o...
- Detailed Description
PRIMARY OBJECTIVE:
Part 1: To determine the maximum tolerated dose (MTD) of tazemetostat in combination with CPX-351 in patients with relapsed/refractory (R/R)-acute myeloid leukemia (AML).
Part 2: To determine the maximum tolerated dose (MTD) of palbociclib in combination with CPX-351 in patients with R/R-AML.
SECONDARY OBJECTIVE:
...
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 24
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Provide signed and dated informed consent form
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Willing to comply with all study procedures and be available for the duration of the study
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Male or female >= 18 years of age
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Histologically confirmed acute myeloid leukemia (non-M3) relapsed from or refractory to at least 1 prior line of therapy. Bone marrow aspirate and biopsy within 28 days of screening is acceptable. If no prior bone marrow biopsy is available, bone marrow biopsy must be performed during screening unless:
* If the subject has >= 20% myeloblasts present in the peripheral blood, a bone marrow biopsy is not necessary to meet this criterion
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Treatment with a prior investigational agent is acceptable so long as it has not been administered within 2 weeks of enrollment and any prior adverse effects have resolved to grade 1 or less with the exception of alopecia
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Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less
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Life expectancy of at least 4 weeks
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Must be able to consume oral medication
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Subjects must have recovered from the toxic effect of any prior therapy to =< grade 1 (except alopecia)
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Creatine clearance (CrCL) >= 45
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Total bilirubin < 2 x upper limit of normal (ULN)
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Female subjects of childbearing age must have a negative pregnancy test
- Subjects with acute promyelocytic leukemia
- Subjects receiving any active chemotherapy agents (except hydroxyurea). Intrathecal methotrexate and cytarabine are permissible
- Subjects whose participation would result in a total cumulative dose of daunorubicin greater than 550 mg/m^2 or greater than 450 mg/m^2 if they previously received mediastinal radiation
- Subjects with evidence of active central nervous system (CNS) leukemia involvement. Lumbar puncture is not required for enrollment in the absence of neurologic symptoms
- Subjects must not be receiving growth factors (except erythropoietin)
- Subjects with currently active second malignancy with the exception of nonmelanoma skin cancer, carcinoma in situ of the cervix, resected prostate cancer with Gleason score =< 6
- Subjects with unstable cardiac disease or uncontrolled arrhythmia
- Subjects with other severe concurrent disease which, in the judgement of the investigator, would make the patient inappropriate to receive high-intensity therapy
- Subjects who are pregnant or breastfeeding
- Subjects with known allergic reactions to components of the study product(s)
- Anything that would place the individual at increased risk or preclude the individual's full compliance with or completion of the study
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part II (palbociclib, CPX-351) Liposome-encapsulated Daunorubicin-Cytarabine Patients receive palbociclib PO QD on days -3 to -1, and CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients also undergo bone marrow aspiration and biopsy and blood sample collection during screening and on study. Part II (palbociclib, CPX-351) Bone Marrow Aspiration and Biopsy Patients receive palbociclib PO QD on days -3 to -1, and CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients also undergo bone marrow aspiration and biopsy and blood sample collection during screening and on study. Part I (tazemetostat, CPX-351) Liposome-encapsulated Daunorubicin-Cytarabine Patients receive tazemetostat PO BID on days -1 to 6, and CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients also undergo bone marrow aspiration and biopsy and blood sample collection during screening and on study. Part I (tazemetostat, CPX-351) Biospecimen Collection Patients receive tazemetostat PO BID on days -1 to 6, and CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients also undergo bone marrow aspiration and biopsy and blood sample collection during screening and on study. Part I (tazemetostat, CPX-351) Bone Marrow Aspiration and Biopsy Patients receive tazemetostat PO BID on days -1 to 6, and CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients also undergo bone marrow aspiration and biopsy and blood sample collection during screening and on study. Part II (palbociclib, CPX-351) Biospecimen Collection Patients receive palbociclib PO QD on days -3 to -1, and CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients also undergo bone marrow aspiration and biopsy and blood sample collection during screening and on study. Part II (palbociclib, CPX-351) Palbociclib Patients receive palbociclib PO QD on days -3 to -1, and CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients also undergo bone marrow aspiration and biopsy and blood sample collection during screening and on study. Part I (tazemetostat, CPX-351) Tazemetostat Patients receive tazemetostat PO BID on days -1 to 6, and CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients also undergo bone marrow aspiration and biopsy and blood sample collection during screening and on study.
- Primary Outcome Measures
Name Time Method Incidence of grade >= 3 non-hematologic dose limiting toxicities Up to 1 year The primary outcome measure will be grade \>= 3 non-hematologic dose limiting toxicities. Adverse events will be coded by organ system and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 5.0. the calculation of adverse events incidences will be passed on number of patients per adverse event category. Standard propo...
- Secondary Outcome Measures
Name Time Method Partial remission (PR) Up to 1 year PR is defined as decrease of at least 50% in the percentage of bone marrow blasts to 5% - 25% and normalization of blood counts.
Relapse free survival The time measured in months to relapse from day 1 of treatment, assessed up to 1 year 95% confidence intervals will be calculated using Kaplan-Meier method.
Complete response Up to 1 year Morphologic leukemia-free state: \< 5% blasts in bone marrow, no blasts with Auer rods or persistence of extramedullary disease. Morphologic complete response (CR): \< 5% blasts in bone marrow with transfusion independence, absolute neutrophil count (ANC) \> 1.0 x 10\^9/L, platelets \>= 100 x10\^9/L. CR without minimal residual disease: morphologic CR with n...
Relapse Up to 1 year Relapse is defined as reappearance of leukemic blasts in the peripheral blood or \> 5% blasts in the bone marrow not attributable to other cause (e.g., bone marrow regeneration after chemotherapy) or extramedullary relapse.
Overall survival The time measured in months from day 1 of treatment, assessed up to 1 year 95% confidence intervals will be calculated using Kaplan-Meier method.
Time to transplant The time measured in months to allogeneic stem cell transplantation from day 1 of treatment, assessed up to 1 year 95% confidence intervals will be calculated using Kaplan-Meier method.
Incidence of adverse events Up to 1 year Assessment of safety and tolerability: Incidence, nature, and severity of adverse events and incidence, nature and severity of treatment-emergent adverse events. The primary outcome measure will be grade \>= 3 non-hematologic dose limiting toxicities. Adverse events will be coded by organ system and graded according to the CTCAE v. 5.0. the calculation of ad...
Induction failure/refractory acute myeloid leukemia (AML) Up to 1 year Induction failure/refractory AML defined as failure to attain CR or CRi.
Time to blood count recovery The number of days until ANC > 1.0 x 10^9/L and platelets >= 100 x 10^9/L from day 1 of treatment, assessed up to 1 year 95% confidence intervals will be calculated using Kaplan-Meier method.
Rate of allogeneic stem cell transplantation Up to 1 year Defined as the proportion of patients who undergo allogeneic stem cell transplantation during the study period.
Trial Locations
- Locations (1)
Thomas Jefferson University Hospital
🇺🇸Philadelphia, Pennsylvania, United States